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https://www.readbyqxmd.com/read/28097824/mechanisms-of-metabolic-memory-and-renal-hypoxia-as-a-therapeutic-target-in-diabetic-kidney-disease
#1
REVIEW
Yosuke Hirakawa, Tetsuhiro Tanaka, Masaomi Nangaku
Diabetic kidney disease (DKD) is a worldwide public health problem. The definition of DKD is being under discussion. Although the term DKD was originally defined as "kidney disease specific to diabetes", DKD frequently means chronic kidney disease (CKD) with diabetes mellitus and includes not only classical diabetic nephropathy, but also kidney dysfunction due to nephrosclerosis and other causes. Metabolic memory plays a crucial role in the progression of various complications of diabetes, including DKD. The mechanisms of metabolic memory in DKD are supposed to include advanced glycation end products, DNA methylation, histone modifications, and non-coding RNA including microRNA...
January 17, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28094382/the-supercoiling-state-of-dna-determines-the-handedness-of-both-h3-and-cenp-a-nucleosomes
#2
R Vlijm, S H Kim, P L De Zwart, Y Dalal, C Dekker
Nucleosomes form the unit structure of the genome in eukaryotes, thereby constituting a fundamental tenet of chromatin biology. In canonical nucleosomes, DNA wraps around the histone octamer in a left-handed toroidal ramp. Here, in single-molecule magnetic tweezers studies of chaperone-assisted nucleosome assembly, we show that the handedness of the DNA wrapping around the nucleosome core is intrinsically ambidextrous, and depends on the pre-assembly supercoiling state of the DNA, i.e., it is not uniquely determined by the octameric histone core...
January 17, 2017: Nanoscale
https://www.readbyqxmd.com/read/28074868/nucleoplasmin-like-domain-of-fkbp39-from-drosophila-melanogaster-forms-a-tetramer-with-partly-disordered-tentacle-like-c-terminal-segments
#3
Małgorzata Kozłowska, Aneta Tarczewska, Michał Jakób, Dominika Bystranowska, Michał Taube, Maciej Kozak, Mariusz Czarnocki-Cieciura, Andrzej Dziembowski, Marek Orłowski, Katarzyna Tkocz, Andrzej Ożyhar
Nucleoplasmins are a nuclear chaperone family defined by the presence of a highly conserved N-terminal core domain. X-ray crystallographic studies of isolated nucleoplasmin core domains revealed a β-propeller structure consisting of a set of five monomers that together form a stable pentamer. Recent studies on isolated N-terminal domains from Drosophila 39-kDa FK506-binding protein (FKBP39) and from other chromatin-associated proteins showed analogous, nucleoplasmin-like (NPL) pentameric structures. Here, we report that the NPL domain of the full-length FKBP39 does not form pentameric complexes...
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28072526/type-i-dna-topoisomerases
#4
Giovanni Capranico, Jessica Marinello, Giovanni Chillemi
DNA topoisomerases constitute a large family of essential enzymes in all domains of life. Even though they share the general reaction chemistry and the ability to govern DNA topology and resolve strand entanglements during fundamental molecular processes, they are characterized by differences in structural organization, modes of enzymatic catalysis and biological functions. Moreover, hundreds of compounds are known to interfere with bacterial and/or eukaryotic enzymes, and some of them are effective drugs for the treatment of infectious diseases and cancers...
January 10, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28067271/praja1-e3-ubiquitin-ligase-promotes-skeletal-myogenesis-through-degradation-of-ezh2-upon-p38%C3%AE-activation
#5
Silvia Consalvi, Arianna Brancaccio, Alessandra Dall'Agnese, Pier Lorenzo Puri, Daniela Palacios
Polycomb proteins are critical chromatin modifiers that regulate stem cell differentiation via transcriptional repression. In skeletal muscle progenitors Enhancer of zeste homologue 2 (EZH2), the catalytic subunit of Polycomb Repressive Complex 2 (PRC2), contributes to maintain the chromatin of muscle genes in a repressive conformation, whereas its down-regulation allows the progression through the myogenic programme. Here, we show that p38α kinase promotes EZH2 degradation in differentiating muscle cells through phosphorylation of threonine 372...
January 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28056762/hic-bench-comprehensive-and-reproducible-hi-c-data-analysis-designed-for-parameter-exploration-and-benchmarking
#6
Charalampos Lazaris, Stephen Kelly, Panagiotis Ntziachristos, Iannis Aifantis, Aristotelis Tsirigos
BACKGROUND: Chromatin conformation capture techniques have evolved rapidly over the last few years and have provided new insights into genome organization at an unprecedented resolution. Analysis of Hi-C data is complex and computationally intensive involving multiple tasks and requiring robust quality assessment. This has led to the development of several tools and methods for processing Hi-C data. However, most of the existing tools do not cover all aspects of the analysis and only offer few quality assessment options...
January 5, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28056052/the-glucocorticoid-receptor-regulates-the-angptl4-gene-in-a-ctcf-mediated-chromatin-context-in-human-hepatic-cells
#7
Masafumi Nakamoto, Ko Ishihara, Takehisa Watanabe, Akiyuki Hirosue, Shinjiro Hino, Masanori Shinohara, Hideki Nakayama, Mitsuyoshi Nakao
Glucocorticoid signaling through the glucocorticoid receptor (GR) plays essential roles in the response to stress and in energy metabolism. This hormonal action is integrated to the transcriptional control of GR-target genes in a cell type-specific and condition-dependent manner. In the present study, we found that the GR regulates the angiopoietin-like 4 gene (ANGPTL4) in a CCCTC-binding factor (CTCF)-mediated chromatin context in the human hepatic HepG2 cells. There are at least four CTCF-enriched sites and two GR-binding sites within the ANGPTL4 locus...
2017: PloS One
https://www.readbyqxmd.com/read/28042859/a-novel-role-of-silibinin-as-a-putative-epigenetic-modulator-in-human-prostate-carcinoma
#8
Ioannis Anestopoulos, Aristeidis P Sfakianos, Rodrigo Franco, Katerina Chlichlia, Mihalis I Panayiotidis, David J Kroll, Aglaia Pappa
Silibinin, extracted from milk thistle (Silybum marianum L.), has exhibited considerable preclinical activity against prostate carcinoma. Its antitumor and chemopreventive activities have been associated with diverse effects on cell cycle, apoptosis, and receptor-dependent mitogenic signaling pathways. Here we hypothesized that silibinin's pleiotropic effects may reflect its interference with epigenetic mechanisms in human prostate cancer cells. More specifically, we have demonstrated that silibinin reduces gene expression levels of the Polycomb Repressive Complex 2 (PRC2) members Enhancer of Zeste Homolog 2 (EZH2), Suppressor of Zeste Homolog 12 (SUZ12), and Embryonic Ectoderm Development (EED) in DU145 and PC3 human prostate cancer cells, as evidenced by Real Time Polymerase Chain Reaction (RT-PCR)...
December 31, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28038734/partially-assembled-nucleosome-structures-at%C3%A2-atomic-detail
#9
Georgy N Rychkov, Andrey V Ilatovskiy, Igor B Nazarov, Alexey V Shvetsov, Dmitry V Lebedev, Alexander Y Konev, Vladimir V Isaev-Ivanov, Alexey V Onufriev
The evidence is now overwhelming that partially assembled nucleosome states (PANS) are as important as the canonical nucleosome structure for the understanding of how accessibility to genomic DNA is regulated in cells. We use a combination of molecular dynamics simulation and atomic force microscopy to deliver, in atomic detail, structural models of three key PANS: the hexasome (H2A·H2B)·(H3·H4)2, the tetrasome (H3·H4)2, and the disome (H3·H4). Despite fluctuations of the conformation of the free DNA in these structures, regions of protected DNA in close contact with the histone core remain stable, thus establishing the basis for the understanding of the role of PANS in DNA accessibility regulation...
December 27, 2016: Biophysical Journal
https://www.readbyqxmd.com/read/28035761/analysis-of-swi-formation-and-propagation-events
#10
Zhiqiang Du, Dustin Kenneth Goncharoff, Xudong Cheng, Liming Li
The budding yeast, Saccharomyces cerevisiae, harbors several prions that are transmitted as altered, heritable protein conformations. [SWI(+) ] is one such prion whose determinant is Swi1, a subunit of the evolutionarily conserved chromatin-remodeling complex SWI/SNF. Despite the importance of Swi1, the molecular events that lead to [SWI(+) ] prionogenesis remain poorly understood. In this study, we have constructed floccullin-promoter-based URA3 reporters for [SWI(+) ] identification. Using these reporters, we show that the spontaneous formation frequency of [SWI(+) ] is significantly higher than that of [PSI(+) ] (prion form of Sup35)...
December 30, 2016: Molecular Microbiology
https://www.readbyqxmd.com/read/28028239/asymmetric-unwrapping-of-nucleosomal-dna-propagates-asymmetric-opening-and-dissociation-of-the-histone-core
#11
Yujie Chen, Joshua M Tokuda, Traci Topping, Steve P Meisburger, Suzette A Pabit, Lisa M Gloss, Lois Pollack
The nucleosome core particle (NCP) is the basic structural unit for genome packaging in eukaryotic cells and consists of DNA wound around a core of eight histone proteins. DNA access is modulated through dynamic processes of NCP disassembly. Partly disassembled structures, such as the hexasome (containing six histones) and the tetrasome (four histones), are important for transcription regulation in vivo. However, the pathways for their formation have been difficult to characterize. We combine time-resolved (TR) small-angle X-ray scattering and TR-FRET to correlate changes in the DNA conformations with composition of the histone core during salt-induced disassembly of canonical NCPs...
December 27, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28027298/inferential-structure-determination-of-chromosomes-from-single-cell-hi-c-data
#12
Simeon Carstens, Michael Nilges, Michael Habeck
Chromosome conformation capture (3C) techniques have revealed many fascinating insights into the spatial organization of genomes. 3C methods typically provide information about chromosomal contacts in a large population of cells, which makes it difficult to draw conclusions about the three-dimensional organization of genomes in individual cells. Recently it became possible to study single cells with Hi-C, a genome-wide 3C variant, demonstrating a high cell-to-cell variability of genome organization. In principle, restraint-based modeling should allow us to infer the 3D structure of chromosomes from single-cell contact data, but suffers from the sparsity and low resolution of chromosomal contacts...
December 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/28024297/variable-chromatin-structure-revealed-by-in-situ-spatially-correlated-dna-cleavage-mapping
#13
Viviana I Risca, Sarah K Denny, Aaron F Straight, William J Greenleaf
Chromatin structure at the length scale encompassing local nucleosome-nucleosome interactions is thought to play a crucial role in regulating transcription and access to DNA. However, this secondary structure of chromatin remains poorly understood compared with the primary structure of single nucleosomes or the tertiary structure of long-range looping interactions. Here we report the first genome-wide map of chromatin conformation in human cells at the 1-3 nucleosome (50-500 bp) scale, obtained using ionizing radiation-induced spatially correlated cleavage of DNA with sequencing (RICC-seq) to identify DNA-DNA contacts that are spatially proximal...
December 26, 2016: Nature
https://www.readbyqxmd.com/read/27994014/human-ap-endonuclease-ape1-is-acetylated-at-dna-damage-sites-in-chromatin-and-acetylation-modulates-its-dna-repair-activity
#14
Shrabasti Roychoudhury, Somsubhra Nath, Heyu Song, Muralidhar L Hegde, Larry J Bellot, Anil K Mantha, Shiladitya Sengupta, Sutapa Ray, Amarnath Natarajan, Kishor K Bhakat
Apurinic/apyrimidinic (AP) sites, the most frequently formed DNA lesions in the genome, inhibit transcription and block replication. The primary enzyme to repair AP sites in mammalian cells is the AP endonuclease (APE1), which functions through the Base Excision Repair (BER) pathway. Although the mechanism by which APE1 repairs AP sites in vitro has been extensively investigated, it is largely unknown how APE1 repairs AP sites in cells. Here, we show that APE1 is acetylated (AcAPE1) after binding to the AP sites in chromatin and that AcAPE1 is exclusively present on chromatin throughout the cell cycle...
December 19, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27979589/in-vitro-hydroquinone-induced-instauration-of-histone-bivalent-mark-on-human-retroelements-line-1-in-hl60-cells
#15
Monica Mancini, Martina Mandruzzato, Alba C Garzia, Nora Sahnane, Elena Magnani, Filippo Macchi, Mustapha Oulad-Abdelghani, Pierre Oudet, Valentina Bollati, Silvia Fustinoni, Daniela Furlan, Ian M Bonapace
Benzene is extensively used in industry despite its leukemogenic activity, representing a significant occupational hazard. We investigated if long-term treatment with low-doses hydroquinone (HQ), a benzene metabolite, might be sufficient to alter in vitro the epigenetic signature underlining LINE-1 sequences, a poorly explored step in health risks associated with benzene exposure. In HL-60 cell line, exploring the epigenetic events occurring in chromatin, we found the transient instauration of the distinctive signature combining the repressive H3Lys27 tri-methylation mark and the activating H3Lys4 tri-methylation mark (H3K27me3/H3K4me3), indicating a tendency toward a poised chromatin conformation...
December 13, 2016: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/27974213/reversal-of-defective-mitochondrial-biogenesis-in-limb-girdle-muscular-dystrophy-2d-by-independent-modulation-of-histone-and-pgc-1%C3%AE-acetylation
#16
Sarah Pambianco, Matteo Giovarelli, Cristiana Perrotta, Silvia Zecchini, Davide Cervia, Ilaria Di Renzo, Claudia Moscheni, Michela Ripolone, Raffaella Violano, Maurizio Moggio, Maria Teresa Bassi, Pier Lorenzo Puri, Lucia Latella, Emilio Clementi, Clara De Palma
Mitochondrial dysfunction occurs in many muscle degenerative disorders. Here, we demonstrate that mitochondrial biogenesis was impaired in limb-girdle muscular dystrophy (LGMD) 2D patients and mice and was associated with impaired OxPhos capacity. Two distinct approaches that modulated histones or peroxisome proliferator-activated receptor-gamma coactivator 1 α (PGC-1α) acetylation exerted equivalent functional effects by targeting different mitochondrial pathways (mitochondrial biogenesis or fatty acid oxidation[FAO])...
December 13, 2016: Cell Reports
https://www.readbyqxmd.com/read/27960448/exploring-nucleosome-unwrapping-using-dna-origami
#17
Jonas J Funke, Philip Ketterer, Corinna Lieleg, Philipp Korber, Hendrik Dietz
We establish a DNA origami based tool for quantifying conformational equilibria of biomolecular assemblies as a function of environmental conditions. As first application, we employed the tool to study the salt-induced disassembly of nucleosome core particles. To extract binding constants and energetic penalties, we integrated nucleosomes in the spectrometer such that unwrapping of the nucleosomal template DNA, leading from bent to more extended states was directly coupled to the conformation of the spectrometer...
December 14, 2016: Nano Letters
https://www.readbyqxmd.com/read/27960036/emerin-self-assembly-mechanism-role-of-the-lem-domain
#18
Camille Samson, Florian Celli, Kitty Hendriks, Maximilian Zinke, Nada Essawy, Isaline Herrada, Ana-Andreea Arteni, François-Xavier Theillet, Béatrice Alpha-Bazin, Jean Armengaud, Catherine Coirault, Adam Lange, Sophie Zinn-Justin
At the nuclear envelope, the inner nuclear membrane protein emerin contributes to the interface between the nucleoskeleton and the chromatin. Emerin is an essential actor of the nuclear response to a mechanical signal. Genetic defects in emerin cause Emery-Dreifuss muscular dystrophy. It was proposed that emerin oligomerization regulates nucleoskeleton binding and impaired oligomerization contributes to the loss of function of emerin disease-causing mutants. We here report the first structural characterization of emerin oligomers...
December 13, 2016: FEBS Journal
https://www.readbyqxmd.com/read/27940491/capturing-native-interactions-intrinsic%C3%A2-methods-to-study-chromatin%C3%A2-conformation
#19
M Jordan Rowley, Victor G Corces
No abstract text is available yet for this article.
December 9, 2016: Molecular Systems Biology
https://www.readbyqxmd.com/read/27940490/exploiting-native-forces-to-capture-chromosome-conformation-in-mammalian-cell-nuclei
#20
Lilija Brant, Theodore Georgomanolis, Milos Nikolic, Chris A Brackley, Petros Kolovos, Wilfred van Ijcken, Frank G Grosveld, Davide Marenduzzo, Argyris Papantonis
Mammalian interphase chromosomes fold into a multitude of loops to fit the confines of cell nuclei, and looping is tightly linked to regulated function. Chromosome conformation capture (3C) technology has significantly advanced our understanding of this structure-to-function relationship. However, all 3C-based methods rely on chemical cross-linking to stabilize spatial interactions. This step remains a "black box" as regards the biases it may introduce, and some discrepancies between microscopy and 3C studies have now been reported...
December 9, 2016: Molecular Systems Biology
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